Confocal DNA cytometry uses 3D images of nuclei stained quantitatively for DNA; nuclear DNA content, size, shape, and chromatin texture are measured and used to derive a quantitative nuclear grade (QNG). QNG measures abnormalities in cancer nuclei, and changes in QNG have been correlated to increasing genomic instability and more aggressive tumor behavior. QNG provides significant and independent prognostic information when compared to established markers of risk such as the Gleason Score. With respect to prostate adenocarcinoma (PCa), this information may be most useful in describing PCa with more prevalent intermediate Gleason scores (6 and 7). If the biology of PCa varies with age, race and ethnicity, QNG should detect such changes. Three areas might be useful in different clinical scenarios unique to the age or racial/ethnic groups of the affected individuals: 1) Detection. Analysis of malignancy associated changes in normal appearing nuclei adjacent to carcinomas might enhance the usefulness of core needle biopsies. 2) Diagnosis. QNG might provide additional independent information to supplement Gleason grades and pathologic stages. 3) Prognosis. QNG might allow greater sensitivity for the prediction of occult extraprostatic extension, recurrence and/or responsiveness to therapy. Malignancy associated changes are important in understanding progressive changes in normal appearing cells with the development of neoplasia and with age, race, and ethnicity. More careful surveillance, delineation of high-risk cohorts for chemoprevention studies, and detection of clinically insignificant cancer might all be different for elderly vs. younger men and in different racial/ethnic groups; these issues must be explored thoroughly. The ability of QNG to detect biological changes with age, race and ethnicity also should be complemented by phenotypic expression of selected molecular markers which correlate with proliferation, apoptosis and/or prognosis. In all age groups, predicting the biological aggressiveness and stage of tumors, based on needle biopsy findings and/or on the results of radical specimens, is critical for clinical decision making. We will use the levels of QNG and molecular markers to predict the aggressiveness of PCa based on age/race and ethnicity. We will test the negative hypothesis that age and ethnic groups, with all other prognostic variables being equal, will have no correlation with tumor aggressiveness.